The effectiveness of Bupivacaine as a pre-emptivepudendal block among patients undergoing vaginal surgeries: meta-analysis of randomized controlled trials

Background: Pre-emptive analgesia using pudendal nerve block (PNB) with bupivacaine is commonly used in clinical practice during pelvic floor and vaginal surgeries. However, its effectiveness is unclear. To update the evidence base we summarised short- and intermediate-term outcomes of preemptive analgesia using pudendal nerve block with bupivacaine as an approach in the management of pelvic floor and vaginal surgeries. Methods: We searched the CENTRAL, PubMed, ClinicalTrials.gov, google scholar and Open Grey from inception until April 2019. The citation lists of relevant papers were also searched. Randomized controlled trials (RCTs) of women who underwent perineal, pelvic floor or vaginal surgeries and received pre-emptive analgesia using a pudendal nerve block were included. Two authors independently screened and selected eligible trials as well as performed data extraction and quality assessment. Disagreements were resolved via consensus and an adjudicator was involved when consensus was not achieved. Data was narratively synthesized, when possible, data was pooled in RevMan 5 using random effects model. Results: Four RCTs with a total of 349 participants were eligible for inclusion. We found evidence of small effect for improvement in post-operative pain scores; requirements for opioids, SMD: -0.89 (95% CI: -1.19, -0.59) and non-steroidal anti-inflammatories SMD -1.04 (95% CI: -1.64, -0.43) in favour of the PNB versus control group. The risk ratio for adverse effects 0.42 (95% CI: 0.18, 0.99) favoured PNB. There was no significant difference between groups for length of hospital stay, MD: -0.82 (95% CI: -5.34, 3.69) and return to normal activity. Conclusion:We found inconclusive evidence that pre-emptive pudendal block using bupivacaine may improve postoperative pain and recovery in perineal, pelvic floor or vaginal surgeries. However, due to the scant and poor quality of evidence included in this systematic review, well-designed and adequately powered RCTs that adhere to reporting guidelines and evaluate key outcomes are needed to inform clinical guidelines on the use of pre-emptive pudendal block. trials evaluating pre-emptive analgesia administered as a PNB for vaginal surgery. derivatives and stage of prolapse; sample size; study attrition; duration of follow-up; inception time (time between presentation and recruitment to trial); type of intervention (dosage, type of nerve block, frequency of administration and approach or method of delivery); outcome measures such as adverse effects and effect estimates [means (standard deviations) or median (ranges)] if provided; follow-up times (short, medium and long-term) and statistical analysis methods. Authors of eligible studies were contacted when insufficient data was reported.


Background
Clinical goals of early ambulation, discharge, and rehabilitation in gynecological surgery was introduced approximately two decades ago. [1] In the US, approximately 200,000 women undergo vaginal surgery each year due to pelvic organ prolapse (POP). The prevalence of surgical interventions for POP is projected to rise from 8% to 45% over the next 30 years. [2,3] Postoperative pain after vaginal reconstruction is usually localized to the posterior vulva and perineum. Dull discomfort may also originate from the region of the sacrospinous ligament and pelvic floor.
Postoperative pain management is a vital element of patient care after gynecological vaginal surgeries. [2,4] It has gained prominence in almost all surgical fields, becoming an important fast-track approach to enhance recovery post-surgery. [1] Different multimodal pain management techniques are used to achieve better outcomes. Nerve block with a local anesthetic is a common technique used in various surgeries worldwide. [2] Pudendal nerve block (PNB) is a low-risk, low-cost anesthetic technique, used in obstetric practice to effectively reduce perineal and vaginal discomfort during repair of obstetric lacerations. [12] It is administered at the sacrospinous ligament and provides highly effective and safe anesthesia to the vulva, lower vagina, and perineum. [13,14] Pre-emptive analgesia is also widely used in many surgical procedures such as laparoscopy, haemorrhoidectomy, penile prosthetic surgery and circumcision. [9][10][11] Pre-emptive analgesia is an intervention provided before initiating painful stimuli, which may reduce or prevent subsequent pain.
A number of studies [5][6][7][8] have reported that using an anesthetic to block nerve fibers before trauma prevents hyper excitability in the dorsal horn of the spinal cord, which is believed to be an essential mechanism of central sensitization. Various pre-emptive treatment modalities and their combinations have been used, however adequate pain management to recommended levels have not been established in previous studies. [3][4][5][6][7][8] Some authors suggest that the effects of pre-emptive analgesia may vary according to the type of surgery, and particularly in vaginal surgery there is conflict on efficacy. [12,13] Various gynecological procedures are currently performed under regional nerve block or with local infiltration, such as cervical cerclage, dilatation and evacuation, and perineal procedures. [15] The obstetrician and gynecologist is often responsible for analgesia and sedation during office-based or outpatient procedures. [13,14] Different local anesthetics are used in gynecological practice, including lidocaine, bupivacaine and mepivacaine. [15] Lidocaine and mepivacaine are short acting in duration, with onset of action typically 5 to 10 minutes and duration of action has been reported to be 1 to 2 hours. While bupivacaine is moderate in its duration of action, it has a time of onset of action of 5 minutes, a duration of 4 hours with 2 mg/kg dose up to 7 hours with epinephrine at 3mg/kg dose. [15,16] The pudendal nerve provides the majority of sensations and functions of the external genitals, the urethra, the anus, and perineum. It also controls the external anal sphincter and the sphincter muscles of the bladder. [17,18] The high lipid solubility of Bupivacaine among other protein receptors makes it a commonly used agent for peripheral nerve blocks. [19,20] However, the use of bupivacaine in PNB has shown controversial results. [21,22] Some studies have shown positive outcomes for the effect of bupivacaine on different nerve blocks in the abdominal and perineal region. [9][10][11][12][13][14] However, these results do not show effectiveness when compared against minimum clinical differences in postoperative pain. [3,4,17,18] Pain originates from multiple points during surgery and outcomes with pre-emptive analgesia vary with different surgical approaches. [2,3] For pelvic reconstructive surgeries, evidence of efficacy is uncertain and important considering the rise in the number of these surgeries performed within clinical practice. [2,3] Therefore, evaluating the safety, efficacy and cost-effectiveness of postoperative pain management techniques that enhance patient recovery would have potential implications within clinical practice. [2,3] Our aim was to synthesise evidence from randomized controlled trials evaluating pre-emptive analgesia administered as a PNB for vaginal surgery.

Objective:
To provide evidence-based recommendations on the effectiveness of pudendal nerve block with Bupivacaine among patients undergoing pelvic floor surgery. We evaluated outcomes of postoperative pain, consumption of additional analgesics, adverse effects, recovery time, patient and surgeon satisfaction.

Protocol registration and search strategy
This systematic review was conducted using recommendations by PRISMA guidelines. [23] Details of the study protocol was registered on PROSPERO website http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID = CRD42019118890, registration number: CRD42019118890.

Sources
Electronic databases of PubMed, MEDLINE, ClinicalTrials.gov and Cochrane Central Register of Controlled Trials database were systematically searched from onset until April 2019 using a combination of MeSH terms, keywords and National Institute of Health search filters to develop a sensitive search strategy. In addition, key words of type of participants and interventions were used to search general databases of google scholar and the grey literature (Open Grey). Search terms of gynecologic surgical procedures, pelvic organ prolapse, pelvic floor disorders, anterior and posterior vaginal repair, colpopexy, colpoperineorrhaphy, perineum or perineal surgery and pudendal nerve block or bupivacaine were then combined. No restrictions by language, date or outcomes were applied during the search process. All articles identified were retrieved and uploaded into a reference manager. See Appendix 1 for details of a search strategy.

Inclusion and exclusion criteria
All randomized control trials assessing post-operative outcomes for women diagnosed with pelvic organ prolapse (POP) during clinical assessment, who underwent perineal or vaginal repair surgery were included. The intervention was PNB using bupivacaine compared to a control group consisting of either general anesthesia alone, spinal anesthesia alone with or without injecting normal saline.
Studies that compared anesthetic approaches to pelvic reconstructive surgery, for example, anterior colporrhaphy, posterior colporrhaphy, colpoperineoraphy, enterocele repair were not included in this review. Studies describing or comparing surgical procedures that involve additional laparoscopic procedures or where the procedure involved high nerve involvement like hysterectomy or laparoscopic assisted vaginal hysterectomies were excluded. In addition, studies that enrolled male participants, involved surgical interventions for obstetrics or anal disorders, or measured gluteal pain instead of perineal pain were excluded. Clinical trials delivering nerve block after surgery; using different anesthetic agents like ropivacaine and lidocaine; different routes of local analgesia; evaluating an additional operative procedure like laparoscopy or measuring different outcomes like gluteal pain were excluded. Reviews, letters, observational studies such as case-controls, cohort studies, case reports and case series were also excluded.

Study selection
All articles were transferred into a systematic review web application -Rayyan for independent screening. [24] The titles and abstracts of studies were independently screened by two reviewers (MR and JT) to eliminate irrelevant studies. Differences of opinion were to be resolved by discussion, when consensus was not achieved a third review author (AA) was consulted. Full texts of potentially eligible articles were then independently reviewed using the study inclusion criteria to identify eligible.
At title and abstract screening, if it was unclear whether a study evaluated postoperative pain after perineal or vaginal surgery, postoperative pain scores or primary outcomes of interest, then the study was retained for full text review. At full text review, randomized controlled trials were screened using the study eligibility criteria. Articles that evaluated bupivacaine as pre-emptive analgesia for women undergoing perineal, vaginal or pelvic floor surgery were retained for qualitative synthesis and when possible, depending on the availability of data was meta-analysed.

Data extraction
Two reviewers (MR and JT) independently extracted data from eligible studies using a standardized extraction form, designed using guidance from the Cochrane Handbook for Systematic Reviews of Interventions and piloted before use. [25] The following information were retrieved: study identification, study characteristics, such as author name and year of publication, study type or design, location, setting, inclusion criteria of the population such as age; metabolic index or its derivatives and stage of prolapse; sample size; study attrition; duration of follow-up; inception time (time between presentation and recruitment to trial); type of intervention (dosage, type of nerve block, frequency of administration and approach or method of delivery); outcome measures such as adverse effects and effect estimates [means (standard deviations) or median (ranges)] if provided; follow-up times (short, medium and long-term) and statistical analysis methods. Authors of eligible studies were contacted when insufficient data was reported.

Data synthesis
A narrative synthesis of the results of studies included was presented. When sufficient data was available for homogenous studies or there was no evidence of a major skew, data were pooled in a meta-analysis. For example, where there was strong evidence of skew in continuous data, results from the trial were not meta-analyzed but expressed in narrative format in the main text of the review.
Due to anticipated heterogeneity, meta-analysis was performed using a random effects model with RevMan 5.3 Software (Cochrane IMS). Comparisons of pudendal nerve block versus control as intervention components were considered and meta-analyzed. Mean differences (MD) and standard deviations (SD) were used to provide summary estimates for continuous measures when an outcome was reported by two or more studies using an inverse variance method to estimate the pooled mean difference. Standardized mean differences (SMD) were used when different assessment tools are used to measure the same outcome. Multiple pain assessment time points were defined as short-term for outcomes measured up to and including four weeks after surgery and intermediate term, when outcomes when measured at greater than 4 weeks after surgery. Subgroup analysis were considered for indications of perineal surgery, if there were sufficient trials. For dichotomous outcomes, we used the Mantel-Haenszel method to estimate relevant effect estimates (such a relative risk, risk ratio and odds ratio) and corresponding confidence intervals were calculated. Where ordinal data were used to measure outcomes, for example, satisfaction rates, categories were collapsed, and the data dichotomized.

Assessment of heterogeneity
Studies included in this review were inspected for evidence of clinical heterogeneity, in either the characteristics of the participants, the interventions or the outcomes. Where pooling the studies was appropriate, statistical heterogeneity between the results of different studies was examined by formally checking the results of the Chi 2 test, using a P value of less than 0.05 as evidence of significant heterogeneity. The I 2 statistic was also checked to determine the percentage of total variation across studies that was due to heterogeneity rather than chance. [25] Heterogeneity was explored using the Chi-squared test and I 2 statistic, with a probability value of <0.05 indicating significant heterogeneity. Findings were interpreted as follows: I 2 of 0% to 30%, unimportant heterogeneity; I 2 of 30% to 60%, moderate heterogeneity; I 2 of 50% to 90%, substantial heterogeneity; and I 2 of 75% to 100%, high heterogeneity. In cases with extreme statistical heterogeneity which could not be explained by differences between studies, the estimates were not pooled in the meta-analyses.When possible, publication bias would be assessed using funnel plots to assess the amount of asymmetry in a funnel plot.

Assessment of Study Quality
Risk of bias was independently assessed by two review authors (MR and JT) using the Cochrane risk of bias tool developed by GRADE (Grading of Recommendations, Assessment, Development and Evaluations) collaboration. The domains assessed were random sequence generation (whether the allocation sequence was adequately generated using a computer random number generator and allocation concealment, whether the allocation was adequately concealed, for example, using opaque sealed envelopes. Blinding of participants, personnel and outcome assessors, whether knowledge of the allocated intervention was adequately prevented during the study. This ensures blinding of participants and key personnel as knowledge of the intervention is likely to influence the outcomes; and whether incomplete outcome or missing data were adequately addressed or recorded. Selective outcome reporting checks whether the study is free of selective outcome reporting when compared against a published study protocol. We also checked whether the study was apparently free of other sources of bias that could put it at a high risk of bias, for example, baseline imbalance or bias related to study design) were also verified. Each domain was scored as either low risk (criteria met); unclear risk (not sure whether criteria met, perhaps due to poor reporting standards) or high risk (criteria not met). The effects of publication bias would be considered based on available data (more than 10 studies). Sensitivity analysis was considered to explore the effects of risk of bias on the results.

Assessment of Quality of Evidence
Findings were summarized in a summary of findings table (SoF) using GRADE. Risk of bias, inconsistency, generalizability and imprecision were considered as they influence effect estimates.
Evidence was downgraded for each factor from high to very low using the following guidelines: greater than 25% of the participants are from studies with a high risk of bias; significant heterogeneity is identified or if large differences in magnitude and direction of effects between studies is present; >50% of the participants are outside the target group; and single studies with <400 participants for continuous outcomes or <300 participants for dichotomous outcomes. [26] The GRADE assessment score was downgraded accordingly when any of these factors when judged as present.

Included studies
Four randomized controlled trials [3,4,17,18] met our inclusion criteria and were included in the review. See Table 1. All studies used randomized parallel group designs providing a total of 349 women, but not all data from participants were included in the analysis of every outcome. One study [3] reported incomplete data that was unclear and not available after contact with the primary author. All trials were single center studies, published in English, conducted in the USA [4] , Lebanon [18] , Iran [3] and Kuwait [17] . Power calculations for sample size were reported for all of the included studies and were appropriate. [3,4,17,18] There was significant heterogeneity between studies included in this review and insufficient trials identified to undertake assessment for publication bias.

Risk of bias assessment of included studies
All studies [3,4,17,18] reported randomly allocating participants into groups using computer generated numbers. One study [3] did not report or perform adequate allocation concealment. All studies reported adequate blinding for study participants. Three studies [4,17,18] reported adequately blinding surgeons, while only two studies [4,18] used blinded outcome assessors.
All studies [3,4,17,18] reported adequate methods for all other domains of risk of bias assessment.
There was no indication of other risk of bias due to imbalance or selective outcome reporting.
However, the reporting standards were poor in two [3,17] out of the four [3,4,17,18] studies included in this review. See Table 2.  Table 3. This was mostly due to high risk of bias within individual studies, inconsistency in the direction of results and imprecision due to inadequate number of participants used to evaluate outcomes. No study assessed outcomes of incomplete analgesia, systemic toxicity, hematoma formation, cost-effectiveness analysis and quality of life.

Result of meta-analysis
Primary outcome

Post-operative VAS scores at 24 hours
Three studies [17,18] provided data for post-operative pain but were not combined in a meta-analysis due to substantial heterogeneity. The results of individual studies showed improvement in patient reported pain among women receiving bupivacaine for PNB compared with women in the control group. See Table 4. One study [17] showed standardised mean difference, SMD of -2.56 (95% CI: -3.03, -2.10) in favour of PNB and another study [18] showed SMD of -0.83 (95% CI: -1.37, -0.29).
Data from one study [4] suggested that the results were skewed. The authors [4] reported no significant differences in post-operative pain outcomes between intervention and control groups, median of 3 (range: 0-10). One study [3] did not provide data for their results, even after contacting the corresponding author. The authors narratively reported improvement in the PNB group compared to the control.

Requirement for additional analgesics
Three studies [3,4,18] provided data for assessing the effect of PNB on the requirement for additional analgesics. See Table 5a. We performed a subgroup analysis for additional analgesic requirements.
We found no difference between groups for the requirement for opioids, SMD of -0.49 (95% CI: -1.25, 0.26) and a significant difference SMD: -0.73 (95% CI: -1.45, -0.01) for NSAIDS (non-steroidal antiinflammatories) between the intervention and control groups ( Figure 2). However, results of a sensitivity analysis after excluding the study by Abramov [4] showed significant differences in additional consumption of analgesics in favour of the PNB arm compared to the control arm. For opioids, we found SMD of -0.89 (95% CI: -1.19, -0.59) and for NSAIDS, SMD of -1.04 (95% CI: -1.64, 0.43). See Figure 3. These findings suggest that participants included in the study by Abramov [4] were clinically heterogeneous. However, in both cases, we found significant statistical heterogeneity between studies. (Figure 3).

Adverse events
All four studies [3,4,17,18] provided data that was combined in a meta-analysis. See Table 5b. We evaluated the relative risk (RR) of adverse events for post-operative complications of nausea and vomiting between the PNB and control arms. The RR was 0.42 (95% CI: 0.18, 0.99) (See Figure 4) in favour of PNB. We found no significant statistical heterogeneity between studies.

Length of hospital stay (in hours)
Two studies [4,18] provided data for length of stay that was combined in a meta-analysis. There were no significant differences between mean length of hospital stay between the intervention (PNB) and control arms (See Figure 5). The mean difference, MD was -0.82 (95% CI: -5.34, 3.69) with no difference between the intervention or control groups. We identified substantial statistical heterogeneity between studies.

Discussion
This is the first systematic review and meta-analysis of published randomized control trials investigating pre-emptive analgesia for perineal or pelvic floor surgery. Providing healthcare professionals with a comprehensive summary of outcomes during postoperative care of patients after vaginal surgery. In a review of over 11,000 cases by Moore [6] , the effect of 0.25%, 0.5% and 0.75% bupivacaine was evaluated and found to be satisfactory in caudal, epidural and peripheral nerve block for obstetric, perineal and abdominal surgery. However, this review [6] only included case reports which are not designed to assess the effectiveness of medical interventions due to their propensity to bias.
This systematic review aimed to evaluate the effect of pre-emptive analgesia using bupivacaine as a PNB on pain relief, additional analgesic requirements, adverse events, length of hospital stay and return to normal activity. The concept of pre-emptive analgesia in vaginal surgery aims to use local infiltration for nerve block to reduce pain from the surgical wound in the form of a pudendal block or para-cervical nerve block. After vaginal reconstruction, post-operative pain is frequently defined as pain in the posterior vulva, perineum, and pelvic floor and infrequently as a perception of pelvic cramps. [20][21][22] Effective anesthesia to the vulva, lower vagina, and perineum is usually achieved by pudendal nerve blockade. The results of our meta-analysis showed small benefit on pain levels using PNB, although the evidence is of low quality and studies were clinically heterogeneous.
Pudendal nerve block in vaginal surgery has been used in a diversity of methods and clinical trials. [30][31][32][33] to decrease postoperative pain and use of postoperative opioids (Table 5a and 5b).
Bupivacaine and ropivacaine are local anesthetics that have shown effective and efficient analgesia in vaginal surgeries, although most of these studies describe bupivacaine as well. [19,[20][21][22] In this review, clinical trials on vaginal reconstructive surgeries evaluate pudendal block for preemptive pain control and showed the most consistent effect. [4,17,18] Pain scores were reduced for 24-36 hours by the analgesic effect of pudendal block using bupivacaine. The study by Rouholamin et al [3] reported significant differences in pain within 48 hours when participants who underwent anterior and posterior vaginal wall repair received pudendal block compared with the control group. [3] However, the trial by Abramov and colleagues showed contradictory results [4] . This is probably due to the lower dose (50-75 mg bupivacaine) of local anesthetic compared to the other trials [3,17,18] that showed better effect on pain reduction and postoperative analgesic requirements. This might have also resulted in an insufficient blockade of the nociceptive stimuli in the visceral afferent pain fibers during pelvic floor surgery. Furthermore, the study by Abramov [4] used a heterogeneous group that may underscore the change observed. Patients undergoing pelvic reconstructive surgery were included in the study. However, in the absence of hysterectomy this approach may not be painful enough to produce a noticeable difference between the groups [4] .
The trial by Ismail and colleagues [17] examined the effect of pre-emptive analgesia applied through different methods for posterior colpoperineorrhaphy. The authors [17] used a pre-emptive nerve stimulator guided by bilateral pudendal nerve block and found improved pain relief and reduced opioid use in the intervention group. The trial reported shorter time to return to normal activities compared to the control group and higher patient as well as surgeon satisfaction. In the trial by Khalil and colleagues [18] , pudendal nerve block for postoperative pain management with nerve stimulator guide showed statistically and clinically relevant results on the first and second postoperative days (P values = 0.005 and 0.004) among patients undergoing anterior and posterior vaginal wall repair. [18] However, it is unclear the exact dose of analgesics, the best technique and procedure that would result in superior outcomes.
Overall, there was lower total analgesic consumption, shorter duration of recovery and greater surgeon and patient satisfaction in the pudendal block group. [17,18] However, the pharmacological interventions used to reduce post-operative opioid vary widely and the certainty of the evidence was unclear. In the trial by Abramov [4] , the authors used hydromorphine and ketorolac, while Rouholamin used Morphine consumption [3] , Ismail used pethidine and paracetamol [17] and Khalil reported Tramodol and Ketoprofen. [18] Therefore, we categorized these into sub-groups of opioids and NSAIDs and performed a sensitivity analysis to assess the overall effect size of the both groups. We found an overall effectiveness in favour of the PNB group compared to the control. Across all studies, postoperative nausea and vomiting was reportedly higher in the control group compared to the PNB group. [3,4,17,18] Patient satisfaction was reported to be significantly better in the PNB group than control. [17,18] Surgeon satisfaction was reported as higher in the PNB group compared to the control, but only one RCT provided results for this outcome and data was meta-analysed. [18] However, when we pooled this data in a meta-analysis, we did not find any significant difference in effect estimates.
Similarly, for return to normal activity, non-statistical improvement was reported by individual trials. [17,18] However, overall there was significant heterogeneity between studies and no evidence of a difference in favour of quicker return to normal activity between the PNB and control arms. Some of our results were similar to reports provided by previous studies [16,37] that investigated the use of PNB to reduce the postoperative pain scores and analgesic requirement, but contradictory to other reports [24] . In a trial [16] that evaluated the analgesic effect of 0.25% Bupivacaine on gluteal pain among patients who underwent sacrospinous ligament colpopexy. The authors [16] did not report reduced postoperative pain scores but found significant reduction in pain medication requirement after surgery. [16] In another study authors assessed the effect of extended release bupivacaine also known as liposomal bupivacaine for reducing postoperative pain after robotic colpopexy and posterior repair. [24] The results showed no improvement in postoperative pain or decrease requirements for medications. However, this might be due to higher nerve involvement by robotic use. [24] In 2009, Long and colleagues conducted a clinical trial among women undergoing vaginal surgery who were given 0.50% of bupivacaine using a paracervical approach as a pre-emptive analgesic. The authors reported statistically significant improvement in postoperative pain scores and requirement for narcotics. [37] Limitations.
These results suggest that pre-emptive via PNB might be beneficial for the management of postoperative pain and for reducing analgesic requirement, but its clinical importance remains unclear. [18] Expected disadvantages of pudendal nerve block are incomplete analgesia, systemic toxicity and hematoma formation [3,4,17,18,32] However, these outcomes were not evaluated by studies included in this review and were under-powered to adequately assess these outcomes.
This study was designed using a comprehensive search strategy to reduce the possibility of publication bias. However, studies might have been missed that were not indexed in the databases searched for this review. The methodological quality of most studies were poor due to inadequate designs such as using opaque envelopes for allocation concealment and poor blinding techniques common in single center studies. [25] Furthermore, we took a broad approach when justifying generalizability of the study populations during the process of performing the GRADE assessment for outcomes. Although substantial heterogeneity was identified between studies, we did not downgrade studies for indirectness, which may have introduced uncertainty in the sample estimates and bias in our results.
The evidence used to synthesize findings for this review only included RCTs which represent the highest level of evidence. However, we were limited by the nature of the information provided in these reports that showed poor reporting standards. Three [4,17,18] out of four [3,4,17,18] studies did not report complete study procedures or data in their published paper. Data were missing or wrongly reported, which questions the accuracy of the findings used to synthesize evidence in this review. We were limited by the quantity and quality of studies identified and could not explore the effect of other factors such as a subgroup analysis for the indication of type of approach; perineal or vaginal surgery; time of pain assessment; pudendal block approach (with or without simulator guide and/or anesthetic solution (% of Bupivacaine or mixed). Although, we planned to perform sensitivity analyses to examine the effect of risk of bias on the results in relation to adequate allocation concealment and sources of missing data. There were insufficient trials to undertake these analyses.

Conclusion
This review found some evidence that pre-emptive pudendal blocks for perineal or vaginal surgeries, might be beneficial for reducing postoperative pain, decreasing use of opioids and NSAIDs as well as related side effects. Further research is needed to confirm these conclusions using larger, appropriately designed, double blind, randomized controlled trials that adequately assess and report clinically relevant, objective as well as subjective outcome measures.

-Competing interests
The authors declare that they have no conflict of interests.

-Funding
We would like to thank the research center of King Fahad Medical City for providing the funding for this project. Project No: IRF 019-006.

Corresponding author
All correspondence are to be directed toDrMunazzah Rafique MR, DA and AA developed, refined and designed the research topic.
JT and MR developed the search strategy for the systematic review, carried out data extraction, quality assessment, data synthesis and interpretation of study results.
DA and AA provided methodological and content area expertise during data synthesis of initial reports.
MR, JT, DA and AA contributed to critically appraising the evidence, writing and refining drafts until final approved version was produced.

-Acknowledgements
The clinical training fellowship awarded to Dr Munazzah Rafique supported the development and open access publication of this manuscript. Procedure: After general anesthetic induction, each patient received a 10-mL pudendal nerve block injection on each side as per pudendal block protocol. After 2 hrs, if surgery was still in progress, an additional 5-mL pudendal nerve block was administered on each side. Co-interventions: Analgesic requirements either intravenous hydromorphone or ketorolac consumption.

Tables
Thirty-two participants (63%) from the bupivacaine group and 30 participants (59%) from the saline group received a second pudendal block injection due to prolongation of their surgery beyond 2 hrs. -Return to normal daily activity was significantly (P = .015) shorter in the PNB group compared with GA group (3.6 vs 12.2 days).
-Patient satisfaction was significantly (P = .006) greater in the PNB group.